trandolapril and Stroke

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction.. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years.. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced.. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Coronary Disease; Female; Hospitalization; Humans; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome

Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Efficacy, safety, and tolerability of perindopril are well established in the treatment of hypertension and heart failure. Moreover, large morbidity-mortality trials, such as the EUROPA, PROGRESS, and PREAMI have shown that treatment with perindopril reduces morbidity and mortality and prevents cardiovascular disease in a large range of patients with vascular diseases, whether or not they are hypertensive. Thus, the outcomes of these and other trials support the concept of cardiovascular protective properties of angiotensin-converting enzyme inhibition with perindopril in addition to the obvious blood-pressure-lowering effect. Considering its properties and the clinical evidence on efficacy and tolerability that has been gathered, perindopril should be considered a first-line therapeutic agent in hypertension, heart failure and acute myocardial infarction and a tool of secondary prevention of coronary artery disease.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Indoles; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Perindopril; Prospective Studies; Ramipril; Randomized Controlled Trials as Topic; Risk; Risk Factors; Stroke; Time Factors

Secretory phospholipase A(2) (sPLA(2)) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA(2) for risk stratification in coronary artery disease (CAD).. We measured plasma sPLA(2) activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications.. After multivariable adjustment, sPLA(2) was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13-2.14) and cardiovascular death or heart failure (1.91, 1.20-3.03). In further multivariable assessment, increased activity levels of sPLA(2) were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06-2.04), independent of lipoprotein-associated phospholipase A(2) mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668-0.675, P = 0.01). sPLA(2), N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively).. sPLA(2) activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA(2) as a therapeutic target.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Diseases; Clinical Enzyme Tests; Coronary Disease; Double-Blind Method; Female; Heart Failure; Humans; Indoles; Inflammation; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Necrosis; Phospholipases A2, Secretory; Predictive Value of Tests; Prognosis; Risk Assessment; Stroke

In patients with prior myocardial infarction (MI), beta-blockers reduce mortality by 23% to 40%. However, despite this favorable effect, adverse effects limit compliance to this medication. The purpose of the study was to compare a beta-blocker-based strategy with a heart rate-lowering calcium antagonists-based strategy in patients with prior MI.. We evaluated 7,218 patients with prior MI enrolled in the INternational VErapamil SR-Trandolapril (INVEST) substudy randomized to verapamil-sustained release (SR)- or atenolol-based strategies. Primary outcome was time to first occurrence of death (all-cause), nonfatal MI, or nonfatal stroke. Secondary outcomes included death, total MI (fatal and nonfatal), and total stroke (fatal and nonfatal) considered separately.. During the 2.8 +/- 1.0 years of follow-up, patients assigned to the verapamil-SR-based and atenolol-based strategies had comparable blood pressure control, and the incidence of the primary outcome was equivalent. There was no difference between the 2 strategies for the outcomes of either death or total MI. However, more patients reported excellent/good well-being (82.3% vs 78.0%, P = .02) at 24 months with a trend toward less incidence of angina pectoris (12.0% vs 14.3%, adjusted P = .07), nonfatal stroke (1.4% vs 2.0%; P = .06), and total stroke (2.0% vs 2.5%, P = .18) in the verapamil-SR-based strategy group.. In hypertensive patients with prior MI, a verapamil-SR-based strategy was equivalent to a beta-blocker-based strategy for blood pressure control and prevention of cardiovascular events, with greater subjective feeling of well-being and a trend toward lower incidence of angina pectoris and stroke in the verapamil-SR-based group.

Topics: Adrenergic beta-Antagonists; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Atenolol; Calcium Channel Blockers; Delayed-Action Preparations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension; Indoles; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Risk; Single-Blind Method; Stroke; Verapamil

Data supporting the prognostic significance of high-sensitivity C-reactive protein (hs-CRP) are derived largely from individuals with no overt coronary artery disease or from patients with acute coronary syndromes. In contrast, the ability of hs-CRP to predict outcomes in patients with stable coronary artery disease and the prognostic significance of the Centers for Disease Control/American Heart Association hs-CRP cut points in such a population remain relatively unexplored.. We measured hs-CRP in 3771 patients with stable coronary artery disease from the Prevention of Events With Angiotensin-Converting Enzyme Inhibition (PEACE) trial, a randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor trandolapril. Patients were followed up for a median of 4.8 years for cardiovascular death, myocardial infarction, or stroke, as well as new heart failure and diabetes. After adjustment for baseline characteristics and treatments, higher hs-CRP levels, even >1 mg/L, were associated with a significantly greater risk of cardiovascular death, myocardial infarction, or stroke (hs-CRP 1 to 3 mg/L: adjusted hazard ratio, 1.39; 95% CI, 1.06 to 1.81; P=0.016; hs-CRP >3 mg/L: adjusted hazard ratio, 1.52; 95% CI, 1.15 to 2.02; P=0.003). Similarly, elevated hs-CRP levels were an independent predictor of new heart failure (adjusted P<0.001 for trend) and new diabetes (adjusted P<0.001 for trend). There were no significant interactions between hs-CRP levels and the effects of trandolapril on any of the above outcomes.. In stable coronary artery disease, an elevated hs-CRP level, even >1 mg/L, is a significant predictor of adverse cardiovascular events independently of baseline characteristics and treatments. An elevated hs-CRP does not appear to identify patients with stable coronary artery disease and preserved ejection fraction who derive particular benefit from angiotensin-converting enzyme inhibition.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Coronary Artery Bypass; Coronary Disease; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Reference Standards; Stroke; Survival Analysis

Knowledge of predictors of diabetes mellitus (DM) development in patients with coronary artery disease (CAD) who use antihypertensive therapy could contribute to decreasing this adverse metabolic consequence. This is particularly relevant because the standard of care, beta blockers combined with diuretics, may contribute to adverse metabolic risk. The INternational VErapamil SR-trandolapril STudy compared a calcium antagonist-based (verapamil SR) and a beta-blocker-based (atenolol) strategy with trandolapril and/or hydrochlorothiazide added to control blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry were investigated with regard to newly diagnosed DM during follow-up. Newly diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0% vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p <0.01). Characteristics associated with risk for newly diagnosed DM included United States residence, left ventricular hypertrophy, previous stroke/transient ischemic attack, Hispanic ethnicity, coronary revascularization, hypercholesterolemia, greater body mass index, and higher follow-up systolic BP. Addition of trandolapril to verapamil SR decreased DM risk and addition of hydrochlorothiazide to atenolol increased risk. In conclusion, clinical findings associated with more severe vascular disease and Hispanic ethnicity identify a group at high risk for developing DM, whereas lower on-treatment BP and treatment with verapamil SR-trandolapril attenuated this risk.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Atenolol; Body Mass Index; Calcium Channel Blockers; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Follow-Up Studies; Hispanic or Latino; Humans; Hydrochlorothiazide; Hypercholesterolemia; Hypertrophy, Left Ventricular; Indoles; Ischemic Attack, Transient; Male; Myocardial Revascularization; Residence Characteristics; Risk Factors; Stroke; Systole; Verapamil

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cohort Studies; Coronary Artery Disease; Female; Humans; Hypertension; Indoles; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Treatment Outcome; Verapamil

Women are at greater risk of developing resistant hypertension (RH) than men, yet scarce data exist on RH-associated outcomes in women. We aimed to determine all-cause mortality risk associated with apparent RH (aRH) among women across the spectrum of underlying coronary disease.. We analyzed data from St. James Women Take Heart (WTH; women without coronary disease at baseline), Women's Ischemia Syndrome Evaluation (women with signs/symptoms of ischemia at baseline), and the INternational VErapamil-Trandolapril STudy (INVEST; women with coronary artery disease and hypertension at baseline), totaling 15,108 adult women with no hypertension, non-RH (blood pressure [BP] ≥140/90 mmHg on ≤2 drugs or BP <140/90 mmHg on 1-3 drugs), or aRH (BP ≥140/90 mmHg on ≥3 drugs or anyone on ≥4 drugs) at baseline. The primary outcome was all-cause mortality.. Prevalence of aRH ranged from 0.4% (WTH) to 10.6% (INVEST). Women with aRH, compared to those without, were older, more often black, and more likely to be obese or diabetic. Pooling all cohorts, risk for all-cause death was greater in women with aRH than in women with non-RH (adjusted HR 1.40; 95% CI 1.27-1.55) and women without hypertension (adjusted HR 2.34; 95% CI 1.76-3.11) over a median follow-up of 14.3 years.. aRH prevalence in women varies according to underlying coronary disease, and aRH is associated with a substantial, early, and sustained increased risk of all-cause death. Additional research into early recognition and prevention strategies for RH are needed, especially in black and older women, and those with known cardiovascular risk factors.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Coronary Artery Disease; Drug Resistance; Female; Humans; Hypertension; Indoles; Middle Aged; Myocardial Ischemia; Obesity; Prospective Studies; Risk Factors; Stroke; Treatment Outcome; United States; Verapamil

There is limited information about the safety of chronic nonsteroidal anti-inflammatory drugs (NSAIDs) in hypertensive patients with coronary artery disease.. This was a post hoc analysis from the INternational VErapamil Trandolapril STudy (INVEST), which enrolled patients with hypertension and coronary artery disease. At each visit, patients were asked by the local site investigator if they were currently taking NSAIDs. Patients who reported NSAID use at every visit were defined as chronic NSAID users, while all others (occasional or never users) were defined as nonchronic NSAID users. The primary composite outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Cox regression was used to construct a multivariate analysis for the primary outcome.. There were 882 chronic NSAID users and 21,694 nonchronic NSAID users (n = 14,408 for never users and n=7286 for intermittent users). At a mean follow-up of 2.7 years, the primary outcome occurred at a rate of 4.4 events per 100 patient-years in the chronic NSAID group, versus 3.7 events per 100 patient-years in the nonchronic NSAID group (adjusted hazard ratio [HR] 1.47; 95% confidence interval [CI], 1.19-1.82; P=.0003). This was due to an increase in cardiovascular mortality (adjusted HR 2.26; 95% CI, 1.70-3.01; P<.0001).. Among hypertensive patients with coronary artery disease, chronic self-reported use of NSAIDs was associated with an increased risk of adverse events during long-term follow-up.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Blood Pressure; Celecoxib; Confounding Factors, Epidemiologic; Coronary Artery Disease; Diclofenac; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Ibuprofen; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Myocardial Infarction; Naproxen; Odds Ratio; Proportional Hazards Models; Pyrazoles; Randomized Controlled Trials as Topic; Stroke; Sulfonamides; Verapamil

Our understanding of factors influencing stroke risk among patients with coronary artery disease is incomplete. Accordingly, factors predicting stroke risk in hypertensive, clinically stable coronary artery disease patients were determined with data from the INternational VErapamil SR-trandolapril STudy (INVEST).. The effect of baseline characteristics and on-treatment blood pressure (BP) were analyzed to determine the risk of stroke (fatal or nonfatal) among the 22 576 patients enrolled. Cox proportional-hazards models (unadjusted, adjusted, and time dependent) were used to identify predictors of stroke among subgroups with these characteristics present at entry and on-treatment BP.. Excellent BP control (at 24 months, >70% <140/90 mm Hg) was achieved during 61 835 patient-years of follow-up, as 377 patients had a stroke (6.1 strokes/1000 patient-years) and 28% of those patients had a fatal stroke. Increased age, black race, US residency, and history of prior myocardial infarction, smoking, stroke/transient ischemic attack, arrhythmia, diabetes, and coronary bypass surgery were associated with an increased risk of stroke. Achieving a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg was associated with a decreased risk of stroke. There was no statistically significant difference in stroke risk comparing the verapamil SR-based with the atenolol-based treatment strategy (adjusted hazard ratio=0.87; 95% CI, 0.71 to 1.06; P=0.17).. Among hypertensive patients with chronic coronary artery disease, stroke was an important complication associated with significant mortality. Black race, US residency, and conditions associated with increased vascular disease severity and arrhythmia predicted increased stroke risk, whereas achieving a BP <140/90 mm Hg on treatment predicted a reduced stroke risk.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Atenolol; Black People; Coronary Artery Disease; Databases, Factual; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Stroke; United States; Verapamil

We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD).. Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies.. We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling.. Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk.. In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Humans; Hypertension; Indoles; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Stroke; Verapamil

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Homocysteine; Humans; Hypertension; Indoles; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Stroke; Verapamil; Vitamins

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Indoles; Isoquinolines; Myocardial Infarction; Perindopril; Prodrugs; Quinapril; Ramipril; Stroke; Stroke Volume; Tetrahydroisoquinolines; Treatment Outcome; Ventricular Dysfunction, Left